This training and research award will prepare the candidate for an independent career as a molecular and behavioral neuroscientist using rigorous behavioral and genetic manipulations to analyze the brain circuits underlying the interaction between motivation and cognition. The candidate is an experimental psychologist with significant expertise in the area of animal learning and behavior. Training provided under this award will take place at Columbia University's Departments of Psychiatry and Neuroscience and will enable the candidate to 1) develop laboratory skills in molecular neuroscience; 2) expand his knowledge of molecular genetics and translational neuroscience so that he can independently develop novel scientific ideas, integrate his research findings with current knowledge, and relate them to clinical practice; 3) receive mentorship in professional development; and 4) develop a strong understanding of the ethical issues inherent in the practice of science. The training goals will be accomplished through a program combining practical training, formal mentorship, consultations with experienced independent investigators, coursework, seminar attendance, and professional scientific meetings. The research supported under this award will elucidate the functional neurocircuitry underlying the interaction between motivation and cognition. Deficits in motivation and cognition are present in a number of psychiatric diseases, and a large literature has documented effects of motivational variables on cognitive performance, but the neural basis of these effects is not well understood. The candidate has developed a novel behavioral paradigm for mice in which performance of a discrimination procedure which assesses sustained attention can be modulated on a trial by trial basis by explicitly signaling the probability of reward for correct choices. Using this paradigm as a methodological foundation, the proposed research will use a genetic technique to silence specific neural populations in the basal forebrain, PFC, and striatum to determine the functional neural circuitry which is necessary and sufficient for motivational modulation of sustained attention performance by signaled reward probability. The proposed research will elucidate the functional neural circuitry by which motivation modulates cognition, which will further our understanding of the biology of motivation and cognition, and may give insight into the neural underpinnings of the functional impairments in clinical populations. PUBLIC HEALTH RELEVANCE: Debilitating impairments in motivation and cognition are present in a number of psychiatric diseases, and motivation has been suggested to interact with cognition in producing functional impairment. The present research will elucidate the functional neural circuitry involved in motivational modulation of sustained attention and may provide insight into the neural circuitry involved in functional impairments in patients.